Syndax Pharmaceuticals has announced that investigators at The University of Texas MD Anderson Cancer Center Department of Breast Medical Oncology have started a Phase 1/2 study of its Entinostat along with lapatinib ditosylate (Tykerb) in patients with locally recurrent or distant relapsed metastatic breast cancer.
Entinostat is an oral small molecule selective inhibitor of class I histone deacetylases, which alter the structure of chromatin to control gene expression.
The phase 1 portion of the study will evaluate the safety profile of the combination and identify the appropriate dosing regimen to be used in the phase 2 portion.
Sponsored by MD Anderson, the Phase 1/2 study is being conducted in collaboration with the National Cancer Institute (NCI) Division of Cancer Treatment and Diagnosis, and Glaxo Smith Kline (GSK).
Syndax president and chief executive officer Joanna Horobin said the study represents the company's continued commitment to work with the NCI, as well as industry and academic collaborators, to expand the Entinostat Combinations Overcoming Resistance (ENCORE) platform aimed at overcoming resistance to targeted therapies in breast cancer and other solid tumours.
"With our recently reported positive data in ENCORE 301 targeting ER+ breast cancer and the NCI sponsored study NCT01234532 combining entinostat with Arimidex in ER-, PR-, HER2- triple negative breast cancer, we are pleased to be in a position to provide proof-of-concept clinical data across all segments of breast cancer," Horobin added.
Principal investigator of the study Naoto Ueno said that based on preclinical work conducted by Syndax's collaborators and GSK scientists, they hope Entinostat may be effective in tackling the resistance pathways that contribute to the reduced efficacy of HER2-targeted agents in breast cancer patients progressing on such therapies.
Entinostat has been studied in more than 600 cancer patients where objective tumour responses have been observed in breast and lung cancer and hematologic malignancies.
Previous Phase 2 randomised placebo-controlled studies with Entinostat have reported promising results in combination with aromatase inhibitors in breast cancer (ENCORE 301) and with the EGFR-TKI erlotinib (ENCORE 401) in non-small cell lung cancer.